The present invention relates to novel fat-soluble and stable silicon-containing derivatives of ascorbic acid. The invention also relates in particular to cosmetic and pharmaceutical compositions comprising these novel derivatives, as well as their use.
A number of derivatives of silicon are known. Thus, patent application FR2645863 describes molecular complexes formed of a compound belonging to the silanol family and of an alkali metal or ammonium derivative of an organic or inorganic acid. Molecular combinations are thus obtained which have the advantage of being soluble in water. This document cites in particular the molecular complex formed of a monomethylsilanetriol and of potassium ascorbate. However, as is specified in this document, the stability of these complexes is not very good, in particular when they are in concentrated solution. In particular, they tend to polymerize, which causes their partial insolubilization. A 2,3,5,6-bis(dimethylsilyl)ascorbate or ascorbosilyl is also known from patent application WO96/10575; in this case, it is a precursor of reactive silanol functions and is therefore also unstable.
The aim of the present invention is to provide novel silicon-containing compounds derived from ascorbic acid, the said compounds being fat-soluble and having good stability both in the dry state and in dilute or concentrated solution.
The subject of the invention is therefore novel silicon-containing compounds derived from ascorbic acid, as are defined below.
Another subject of the invention is a method of preparing the compounds of formulae (2) to (4) defined below, by hydrosilylation of the corresponding siloxane or silane derivative represented by one of the formulae (5) to (7) defined below, on an organic derivative of ascorbic acid chosen from the compounds of formula (Ixe2x80x2) defined below, followed by deprotection of the compound obtained, for example by acid hydrolysis of the isopropylidenes and/or debenzylation by catalytic hydrogenation.
Another subject of the invention is a method of preparing the silane derivatives of formula (2) defined below by reacting a derivative of formula (Ixe2x80x2xe2x80x3), defined below, with a silane derivative of the following formula (8) 
in which Hal represents a halogen and more particularly chlorine or iodine and the radicals R1, Rxe2x80x21, Rxe2x80x22. Rxe2x80x23, V, p and q have the same meanings as above.
Yet another subject of the invention is an in particular cosmetic or pharmaceutical composition comprising a cosmetically or pharmaceutically acceptable medium and at least one silicon-containing compound derived from ascorbic acid as defined above.
Another subject of the invention is the use of at least one such silicon-containing compound derived from ascorbic acid as antioxidant and/or anti-free-radical agent, in particular in a cosmetic or pharmaceutical composition.
In particular, this use may be cosmetic for, or in a cosmetic composition intended for, treating oxidative stress and/or treating the effects of exposure to sunlight and/or preventing ageing in particular of the skin, the hair, the eyelashes, the eyebrows and/or the nails.
This use may also be for the preparation of a pharmaceutical composition intended for treating oxidative stress and/or treating the effects of exposure to ionizing or solar radiation, and/or preventing ageing in particular of the skin, of the hair, of the eyelashes, of the eyebrows and/or of the nails, and/or treating the effects of the use of certain medicaments which generate free radicals.
Thus, the applicant has found that by covalently grafting one or more ascorbic acid derivatives onto a silicon-containing chain, novel compounds were obtained which had very good properties of solubility in the customary organic solvents, in particular in fatty substances such as oils, as well as high stability in these media or as such.
Moreover, it was observed that these compounds had excellent cosmetic properties.
The compounds according to the invention are therefore characterized in that
either they consist of a silicone-containing chain comprising at least one unit of formula (1): 
or they are silanes corresponding to the following formula (2):
Axe2x80x94SiRxe2x80x21Rxe2x80x22Rxe2x80x23xe2x80x83xe2x80x83(2)
in which:
R denotes a linear, cyclic or branched, saturated or unsaturated, optionally partially or completely halogenated, C1-C30 hydrocarbon radical or a trimethylsilyloxy group of formula xe2x80x94Oxe2x80x94SiMe3;
a is equal to 1 or 2,
Rxe2x80x21, Rxe2x80x22, Rxe2x80x23, which are identical or different, are chosen from linear or branched C1-C8 alkyl radicals, linear or branched C1-C8 alkenyl radicals, or a trimethylsilyloxy group;
A is a radical of the following formula (I): 
in which L1, L2, L3 and L4 represent hydrogen or a divalent radical of formula (a) or (axe2x80x2) allowing the attachment of the radical A onto the silicon-containing chain, with the proviso that at least one of the radicals L1, L2, L3 and L4, preferably only one of the said radicals L1, L2, L3 and L4, represents the said divalent radical of the following formula (a) or (axe2x80x2): 
in which:
V is a linear or branched, saturated or unsaturated, divalent C1-C6 hydrocarbon radical optionally substituted with a hydroxyl radical or a linear or branched, saturated or unsaturated C2-C8 alkoxy radical;
R1 represents a hydrogen atom, a hydroxyl radical or a linear or branched, saturated or unsaturated C1-C8 hydrocarbon radical;
p is 0 or 1, q is 0 or 1, it being understood that p+q is different from 0.
The compounds according to the invention consisting of a silicone-containing chain comprising at least one unit of formula (1) above therefore comprise in particular at least one unit of formula (1a): 
and/or at least one unit of formula (1b): 
Preferably, they may comprise in addition at least one other unit, for example of the (di-)alkylsiloxane type of formula (1c): 
Thus, they may in particular be represented by one of the following formulae (3) or (4): 
in which:
the radicals B, which are identical or different, are chosen from the radicals R and A,
r is an integer between 0 and 50 inclusive, preferably between 0 and 5,
s is an integer between 0 and 20 inclusive, preferably chosen from 0, 1 or 2, with the proviso that if s=0, then at least one of the two radicals B represents A,
u is an integer between 1 and 6 inclusive, preferably chosen from 1 or 2,
t is an integer between 0 and 9 inclusive, preferably chosen from 2, 3 or 4,
it being understood that t+u is between 3 and 10 inclusive, and is preferably equal to 3, 4, 5 or 6.
Preferably, the radicals R, which are identical or different, are chosen from linear, cyclic or branched, saturated or unsaturated C1-C18 hydrocarbon radicals and linear or branched, saturated or unsaturated, partially halogenated, in particular fluorinated, C1-C8 hydrocarbon radicals.
Still more preferably, the radicals R, which are identical or different, are chosen from linear or branched C1-C10 alkyl radicals, the phenyl radical and the linear or branched fluorinated C1-C8 alkyl radicals.
The methyl and 3,3,3-trifluoropropyl radicals may be mentioned in particular. More particularly, at least 80% in numerical terms of the radicals R are methyl radicals.
Preferably, the radicals Rxe2x80x21, Rxe2x80x22, Rxe2x80x23, which are identical or different, are chosen from linear or branched C1-C6 alkyl radicals, in particular methyl or ethyl radicals, and the trimethylsilyloxy group.
In general, the silicon-containing derivatives corresponding to one of the formulae (1), (2), (3) or (4), and having at least one of the following characteristics will be more particularly preferred:
R is CH3;
B is CH3;
Rxe2x80x21, Rxe2x80x22, Rxe2x80x23 represent CH3 or the trimethylsilyloxy group;
R1 is hydrogen or CH3;
V is xe2x80x94CH2xe2x80x94 or xe2x80x94CH2xe2x80x94CH(OH)CH2xe2x80x94;
p is 1,
r is between 0 and 5 inclusive,
s is between 1 and 2 inclusive,
t+u is between 3 and 6.
Preferably, the divalent radicals corresponding to the formulae (a) or (axe2x80x2) are chosen from linear or branched, saturated or unsaturated, optionally hydroxylated, divalent C1-C6 hydrocarbon radicals such as the methylene (xe2x80x94CH2xe2x80x94), ethylene (xe2x80x94CH2xe2x80x94CH2xe2x80x94), propylene (xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94), n-butylene (xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94) or isobutylene (xe2x80x94CH2xe2x80x94CH(CH3)xe2x80x94CH2xe2x80x94) radicals, and the radicals xe2x80x94CHxe2x95x90CHxe2x80x94CH2xe2x80x94, xe2x80x94CHxe2x95x90C(CH3)xe2x80x94CH2xe2x80x94, xe2x80x94CHxe2x95x90CHxe2x80x94CH(CH3)xe2x80x94 and xe2x80x94CH2xe2x80x94CH(OH)xe2x80x94CH2xe2x80x94.
Among the preferred silicon-containing derivatives corresponding to the formula (1), and more particularly to the formula (3), the following compounds may be mentioned:
5-(1,2-dihydroxyethyl)-3-hydroxy-4-(3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]-propyloxy)-5H-furan-2-one,
5-(1,2-dihydroxyethyl)-4-hydroxy-3-(3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]-propyloxy)-5H-furan-2-one,
5-(1,2-dihydroxyethyl)-3-hydroxy-4-[2-methyl-3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-disiloxanyl]propyloxy]-5H-furan-2-one,
5-(1,2-dihydroxyethyl)-4-hydroxy-3-[2-methyl-3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-disiloxanyl]propyloxy]-5H-furan-2-one,
5-(1,2-dihydroxyethyl)-4-[3-[3-[2-methyl-3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]-propyloxy]-2-hydroxy-propyloxy]-3-hydroxy-5H-furan-2-one and
5-(1,2-dihydroxyethyl)-3-[3-[3-[2-methyl-3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]-propyloxy]-2-hydroxy-propyloxy]-4-hydroxy-5H-furan-2-one.
Among the preferred silicon-containing derivatives corresponding to the formula (2), the following compounds may be mentioned:
5-(1,2-dihydroxyethyl)-3-hydroxy-4-trimethylsilanylmethoxy-5H-furan-2-one,
5-(1,2-dihydroxyethyl)-4-hydroxy-3-(3-trimethylsilanylmethoxy)-5H-furan-2-one,
5-(1,2-dihydroxyethyl)-3-hydroxy-4-(3-trimethylsilanylpropyloxy)-5H-furan-2-one, and
5-(1,2-dihydroxyethyl)-4-hydroxy-3-(3-trimethylsilanylpropyloxy)-5H-furan-2-one
To prepare the derivatives of formulae (1) to (4), the procedure may be conventionally carried out using a hydrosilylation reaction starting with the corresponding siloxane or silane derivative in which for example all the radicals A are hydrogen atoms. This siloxane or silane derivative is called xe2x80x9cSiH-containing derivativexe2x80x9d in the remainder of the present description.
The SiH groups may be present in the chain and/or at the ends of the silicon-containing chain. These SiH-containing derivatives are products which are well known in the silicone industry and are generally commercially available. They are for example described in patents U.S. Pat. No. 3,220,972, U.S. Pat. No. 3,697,473 and U.S. Pat. No. 4,340,709.
The SiH-containing derivatives allowing the preparation of the compounds of formulae (2) to (4) may be represented by the following formulae (5) to (7):
Hxe2x80x94SiRxe2x80x21Rxe2x80x22Rxe2x80x23xe2x80x83xe2x80x83(5)

in which:
Rxe2x80x21, Rxe2x80x22, Rxe2x80x23, R, r, s, t and u have the meaning given above,
Bxe2x80x2, which are identical or different, are chosen from the radicals R and a hydrogen atom, with the proviso that if s=0, then at least one of the two radicals Bxe2x80x2 represents H.
To prepare the compounds according to the invention of formulae (2) to (4) above, the procedure may be carried out in the following manner.
A reaction of hydrosilylation of the SiH-containing derivative of formula (5), (6) or (7) is carried out, preferably in the presence of a catalytically effective quantity of a platinum catalyst, on an organic derivative of ascorbic acid chosen from the compounds of the following formula (Ixe2x80x2): 
in which Lxe2x80x21, Lxe2x80x22, Lxe2x80x23 and Lxe2x80x24 represent benzyloxy groups or correspond to one of the following two formulae (b) and (bxe2x80x2): 
in which R1, V and p have the same meanings as above, it being possible for the radicals Lxe2x80x21 and Lxe2x80x22 in addition to form together with the ascorbic acid residue a methylenedioxy ring substituted with at least one C1-6 alkyl group or a phenyl group, in particular with a methyl, ethyl or phenyl group, or even with two alkyl or phenyl groups;
with the proviso that at least one of the radicals Lxe2x80x21, Lxe2x80x22, Lxe2x80x23 and Lxe2x80x24 represents the radical (b) or (bxe2x80x2).
The hydrosilylation reaction can therefore be carried out according to one of the following two reactions: 
These derivatives (Ixe2x80x2) may in particular be obtained by condensation, in a conventional manner, of an alkene or alkenyl halide with a derivative of formula (Ixe2x80x3): 
in which Lxe2x80x31, Lxe2x80x32, Lxe2x80x33 and Lxe2x80x34 represent benzyloxy groups or a hydrogen atom, with the proviso that at least one of the radicals Lxe2x80x31, Lxe2x80x32, Lxe2x80x33 and Lxe2x80x34 represent hydrogen.
These derivatives of formula (Ixe2x80x3) may be prepared according to the customary procedures which are well known to persons skilled in the art; some are in particular described in patent application EP411184.
After the hydrosilylation of the SiH-containing derivative of formulae (5), (6) or (7) on the ascorbic acid derivative of formula (Ixe2x80x2), it is possible to carry out a deprotection of the compound obtained, according to the conventional deprotection methods known in the literature, for example by acid hydrolysis of the isopropylidenes and/or debenzylation by catalytic hydrogenation.
The compounds of formulae (2) to (4) above according to the invention are then obtained.
Moreover, it is possible to prepare the silane derivatives of formula (2) according to another method of synthesis which consists in reacting:
a derivative of formula (Ixe2x80x2xe2x80x3): 
in which Lxe2x80x31, Lxe2x80x32, Lxe2x80x33 and Lxe2x80x34 represent benzyloxy groups or a hydrogen atom,
it being possible for the radicals Lxe2x80x31, Lxe2x80x32 in addition to form together with the ascorbic acid residue a methylenedioxy ring substituted with at least one C1-6 alkyl group or a phenyl group, in particular with a methyl, ethyl or phenyl group, or even with two alkyl or phenyl groups;
with the proviso that at least one of the radicals Lxe2x80x31, Lxe2x80x32, Lxe2x80x33 and Lxe2x80x34 represents hydrogen,
with a silane derivative of the following formula (8): 
in which Hal represents a halogen and more particularly chlorine or iodine and the radicals R1, Rxe2x80x21, Rxe2x80x22, Rxe2x80x23, V, p and q have the same meanings as above.
The compounds according to the invention are generally present in the compositions of the invention in proportions of between 0.1% and 10% by weight, preferably between 0.5% and 5% by weight, relative to the total weight of the composition.
These compositions, which may in particular be cosmetic or pharmaceutical compositions, therefore comprise moreover a cosmetically or pharmaceutically acceptable medium, that is to say a medium compatible with all keratinous materials such as the skin of the body or of the face, the mucous membranes, the semi-mucous membranes, the scalp as well as the superficial body growths such as the nails, the hair, the eyelashes and the eyebrows.
The compositions according to the invention may be provided in any cosmetically or pharmaceutically acceptable galenic form, such as in the form of a lotion, suspension, dispersion or solution in solvent or aqueous-alcoholic medium, optionally with a multiphase, optionally thickened or even gelled; in the form of a gel, a foam, a spray or an oil-in-water, water-in-oil or multiple emulsion; in the form of a loose, compact or cast powder; or in the form of a solid or an anhydrous paste.
Persons skilled in the art will be able to choose the appropriate galenic form, as well as its method of preparation, based on their general knowledge, taking into account, on the one hand, the nature of the constituents used, in particular their solubility in the carrier, and, on the other hand, the application envisaged for the composition.
Thus, the composition may comprise at least one ingredient chosen from the adjuvants normally used in the field considered, such as fatty substances, organic solvents, water, silicones, thickeners, emollients, sunscreens, antifoams, moisturizing agents, perfumes, preservatives, surfactants, fillers, sequestrants, anionic, cationic, nonionic and/or amphoteric polymers, propellants, alkalinizing or acidifying agents, colorants, pigments or nanopigments, cosmetic active agents.
Among the fatty substances, there may be mentioned oils and/or waxes, in particular of animal, plant, mineral or synthetic origin; C8-C32 fatty acids; C8-C32 fatty acid esters; C8-C32 fatty alcohols. There may be mentioned more particularly petroleum jelly, paraffin, lanolin, hydrogenated lanolin, acetylated lanolin, hydrogenated palm oil, hydrogenated castor oil, liquid paraffin, paraffin oil, Purcellin oil, silicone oils, volatile or otherwise, isoparaffins.
Among the organic solvents, there may be mentioned C1-C6 lower polyols such as ethanol, isopropanol, propylene glycol, glycerin or sorbitol.
Of course, persons skilled in the art will be careful to choose the possible additional compound(s) cited above and/or their quantities such that the advantageous properties intrinsically attached to the compound in accordance with the invention are not, or not substantially, impaired by the addition(s) envisaged.
It has been observed that the compounds of the invention have an excellent fat-solubility, in particular in fatty substances such as Miglyol, alcohols (in particular ethanol), glycols (in particular propylene glycol) and silicone oils (in particular PDMS). Moreover, they become uniformly distributed in conventional cosmetic carriers containing at least one fatty phase or a cosmetically acceptable organic solvent.
Moreover, it has been observed that the compounds according to the invention could exhibit good antioxidant and/or anti-free-radical properties.
They therefore find a very special application in cosmetic or pharmaceutical compositions intended for treating oxidative stress and/or treating the effects of exposure to sunlight and/or preventing ageing in particular of the skin, of the hair, of the eyelashes, of the eyebrows and/or of the nails.
The compositions comprising them therefore find a very special application as a composition to be applied to the skin of the body and/or of the face, and/or to the hair, eyelashes, eyebrows and/or nails.
In particular, these compositions may be present to be used:
as a composition for protecting the human epidermis or the hair against UV radiation (antisun compositions);
as a cosmetic composition for the protection or treatment or care of the hair, in particular in the form of a shampoo, lotion, gel or rinse-off composition, to be applied before or after shampooing, before or after dyeing or bleaching, before, during or after permanent-waving or hair straightening, of a hair-styling or treatment lotion or gel, of a blow-drying or hair-setting lotion or gel, of a hair lacquer, of a composition for permanent-waving or hair straightening, for dyeing or bleaching the hair;
as a care composition for the skin of the body and/or of the face, such as a treatment cream for the epidermis, day cream, night cream, antiwrinkle cream, moisturizing cream, cream for the hands or the feet;
as a makeup composition for the eyelashes, the eyebrows, the hair, the body or the face, such as foundation, lipstick, eyeshadow, blusher, eyeliner, mascara, dyeing gel, nail varnish.